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EP-3423091-B1 - COMPOSITIONS AND METHODS FOR INDUCING HIV-1 ANTIBODIES

EP3423091B1EP 3423091 B1EP3423091 B1EP 3423091B1EP-3423091-B1

Inventors

  • HAYNES, BARTON, F.
  • BONSIGNORI, MATTIA
  • KORBER, BETTE, T.
  • HRABER, Peter, T.
  • SAUNDERS, Kevin

Dates

Publication Date
20260506
Application Date
20170303

Claims (15)

  1. A recombinant HIV-1 envelope polypeptide, wherein the polypeptide comprises
  2. A recombinant HIV-1 envelope polypeptide wherein the polypeptide comprises
  3. A nucleic acid encoding the recombinant HIV-1 envelope polypeptide of claim 1 or claim 2.
  4. An immunogenic composition comprising the recombinant HIV-1 envelope polypeptide of claim 1 or claim 2, and a carrier.
  5. An immunogenic composition comprising the nucleic acid of claim 3 and a carrier.
  6. The immunogenic composition of claim 4 or claim 5 further comprising an adjuvant.
  7. The nucleic acid of claim 3 or the immunogenic composition of claim 5, wherein the nucleic acid is operably linked to a promoter inserted in an expression vector.
  8. The recombinant HIV-1 envelope polypeptide of claim 1 or claim 2, wherein the polypeptide is multimerized in a liposome or nanoparticle.
  9. A composition comprising the recombinant HIV-1 envelope polypeptide of claim 1, the recombinant HIV-1 envelope polypeptide of claim 2, the immunogenic composition of claim 4, or the liposome or nanoparticle of claim 8, for use in inducing an immune response in a subject, wherein the composition is administered in an amount sufficient to induce an immune response and wherein the administration step can alternatively, or in addition, comprise administering any suitable form: a nucleic acid encoding the recombinant HIV-1 envelope polypeptide of claim 1, a nucleic acid encoding the recombinant HIV-1 envelope polypeptide of claim 2, a nucleic acid encoding the recombinant HIV-1 envelope polypeptide of claim 1 and further comprising a carrier, a nucleic acid encoding the recombinant HIV-1 envelope polypeptide of claim 2 and further comprising a carrier, a nucleic acid encoding the recombinant HIV-1 envelope polypeptide of claim 1 and further comprising an adjuvant, or a nucleic acid encoding the recombinant HIV-1 envelope polypeptide of claim 2 and further comprising an adjuvant, in an amount sufficient to induce an immune response.
  10. The composition for use according to claim 9, wherein the nucleic acid encodes a soluble or stabilized protomer of a SOSIP trimer.
  11. The composition for use according to claim 9, wherein the recombinant HIV-1 envelope polypeptide is in the form of a soluble trimer.
  12. The composition for use according to claim 9, wherein the composition further comprises an adjuvant.
  13. The composition for use according to 9, further comprising administering an agent which modulates host immune tolerance.
  14. The composition for use according to claim 9 or 11, wherein the recombinant HIV-1 envelope polypeptide of the composition is multimerized in a liposome or a nanoparticle.
  15. The composition of claim 4, wherein the polypeptide is comprised in a nanoparticle, optionally wherein the nanoparticle comprises ferritin, wherein the ferritin is fused to the recombinant HIV-1 envelope polypeptide.

Description

This application claims the benefit of and priority to U.S. Provisional Application No. 62/303,273 filed March 3, 2016 and U.S. Provisional Application No. 62/403,649 filed October 3. The United States government has certain rights in this invention pursuant to Contract No. DE-AC52-06NA25396 between the United States Department of Energy and Los Alamos National Security, LLC for the operation of Los Alamos National Laboratory. TECHNICAL FIELD The present invention relates, in general, to human immunodeficiency virus (HIV), and, in particular, to HIV-1 immunogenic compositions their methods of making and their use in vaccination regimens. BACKGROUND Development of an effective vaccine for prevention of HIV-1 infection is a global priority. To provide protection, an HIV-1 vaccine should induce broadly neutralizing antibodies (bnAbs). One class of bnAbs among antibodies isolated from infected individuals targets the glycan-polypeptide at the base of the envelope third variable loop (V3). However, BnAbs have not been successfully induced by vaccine constructs thus far. WO2014/172366 A1 describes a vaccine for HIV-1, comprising synthetic V3 glycopeptides, and to methods of making and using same. SUMMARY The invention is set out in the appended claims. Disclosed herein are compositions comprising V3 antibody immunogens and methods for inducing antibodies to the V3 HIV-1 envelope region. Any reference in the description to methods of treatment or in vivo diagnosis refer to the compounds, pharmaceutical compositions and medicaments of the present invention for use in method of treatment of the human or animal body by therapy or for in vivo diagnosis. The disclosure provides a selection of immunogens which are used to induce V3 antibodies. The immunogens include a homogeneous minimal immunogen with high mannose glycans reflective of a native Env V3-glycan bnAb epitope, (Man9-V3). In some embodiments, the immunogens include a homogeneous minimal immunogen without glycans. V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Both fluorophore-labeled Man9-V3 or native-like trimers similarly bound to bnAb memory B cells, and by flow sorting isolated members of a bnAb clonal lineage from an HIV-1-infected individual. The glycopeptide of Figure 38A-E bound the germline of a V3-glycan bnAb lineage. Thus, a Man9-V3 glycopeptide mimics a HIV-1 V3-glycan bnAb epitope and is a candidate immunogen to initiate V3-glycan bnAb lineage maturation. In some embodiments the compositions comprise immunologically and pharmaceutically acceptable carriers and/or excipients. Disclosed herein is a method of inducing an immune response in a subject comprising administering a combination of immunogens comprising V3-peptide and/or glycopeptide, wherein the peptide binds to a UCA of a V3 glycan antibody, HIV-1 envelope CH848.0949.10.17; CH848.0836.10.31; CH848.0358.80.06; CH848.1432.5.41; CH848.0526.25.02 in any suitable form or any combination thereof as a prime and/or boost in an amount sufficient to induce an immune response, wherein the envelope is administered as a polypeptide or a nucleic acid encoding the same. In certain instances, the compositions contemplate nucleic acid, as DNA and/or RNA, or proteins immunogens either alone or in any combination. In certain instances the methods contemplate genetic, as DNA and/or RNA, immunization either alone or in combination with envelope protein(s). In certain instances the nucleic acid encoding an envelope is operably linked to a promoter inserted an expression vector. The compositions may comprise a suitable carrier. In certain aspects the compositions comprise a suitable adjuvant. In certain instances the induced immune response includes induction of antibodies, including but not limited to autologous and/or cross-reactive (broadly) neutralizing antibodies against HIV-1 envelope. Various assays that analyze whether an immunogenic composition induces an immune response, and the type of antibodies induced are known in the art and are also described herein. Disclosed herein is an expression vector comprising any of the nucleic acid sequences of the invention, wherein the nucleic acid is operably linked to a promoter. Disclosed herein is an expression vector comprising a nucleic acid sequence encoding any of the polypeptides of the invention, wherein the nucleic acid is operably linked to a promoter. In certain instances, the nucleic acids are codon optimized for expression in a mammalian cell, in vivo or in vitro. In certain aspects the invention provides nucleic acids comprising any one of the nucleic acid sequences of invention. In certain aspects the invention provides nucleic acids consisting essentially of any one of the nucleic acid sequences of invention. In certain aspects the invention provides nucleic acids consisting of any one of the nucleic acid sequences of invention. In certain embodiments the nucleic acid of the invention, is operab